反应详情

2-[4-(2-Hydroxyethyl)piperazin-l-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (104.94 g, 0.286 mol) was dissolved in tetrahydrofuran (1.4 L), and triethylamine (48.5 g, 0.479 mol), 4-dimethylaminopyridine (1.76 g, 14.4 mmol), and methanesulfonyl chloride (42 g, 0.366 mol) were sequentially added to the solution under cooling with ice, followed by stirring for 1 hour at the same temperature. The reaction mixture was filtrated, and the filtrate was concentrated under reduced pressure, to thereby yield 144.92 g of a pale yellow foamed substance. The product was dissolved in N,N-dimethylformamide (1 L), and 2-mercaptobenzimidazole (48.58 g, 0.323 mol), potassium carbonate (48.58 g, 0.351 mol), and 18-crown-6 (3.56 g, 13.5 mmol) were added to the resultant solution at room temperature, followed by stirring for 3 hours at 80° C. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned by adding chloroform and water. The aqueous layer was extracted with chloroform. The combined organic layer was washed with saturated brine, dried over sodium sulfate anhydrate, and concentrated under reduced pressure. The residue was purified through silica gel column chromatography (developer: hexane/acetone=1/1–1/3), to thereby yield 55.85 g of 2-[4-[2-(benzimidazol-2-ylthio)ethyl]piperazin-1-yl]-N-[2,4-bis(methylthio)-6-methylpyridin-3-yl]acetamide (yield: 39.2%).

1. temperatureunder cooling with ice
2. filtrationThe reaction mixture was filtrated
3. concentrationthe filtrate was concentrated under reduced pressure
4. dissolutionThe product was dissolved in N,N-dimethylformamide (1 L)
5. stirringby stirring for 3 hours at 80° C
6. concentrationThe reaction mixture was concentrated under reduced pressure
7. customthe residue was partitioned
8. additionby adding chloroform and water
9. extractionThe aqueous layer was extracted with chloroform
10. washThe combined organic layer was washed with saturated brine
11. dry with materialdried over sodium sulfate anhydrate
12. concentrationconcentrated under reduced pressure
13. customThe residue was purified through silica gel column chromatography (developer: hexane/acetone=1/1–1/3)